Novel compounds that target lipoprotein lipase and mediate growth arrest in acute lymphoblastic leukemia.
*Acute lymphoblastic leukemia; *Cancer; *Co-culture model; *Lipids; *Lipoprotein lipase; *Metabolism; Amides/chemistry/metabolism/pharmacology; Antineoplastic Agents/*chemistry/metabolism/pharmacology; Binding Sites; Cell Line; Cell Proliferation/drug effects; Coculture Techniques; Dyslipidemias/complications/metabolism/pathology; Humans; Lipoprotein Lipase/antagonists & inhibitors/*metabolism; Mesenchymal Stem Cells/cytology/metabolism; Molecular Docking Simulation; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications/metabolism/pathology; Protein Binding; Protein Structure; Serum Albumin/chemistry/metabolism; Tertiary; Tumor
Over the past decade, the therapeutic strategies employed to treat B-precursor acute lymphoblastic leukemia (ALL) have been progressively successful in treating the disease. Unfortunately, the treatment associated dyslipidemia, either acute or chronic, is very prevalent and a cause for decreased quality of life in the surviving patients. To overcome this hurdle, we tested a series of cylopropanecarboxamides, a family demonstrated to target lipid metabolism, for their anti-leukemic activity in ALL. Several of the compounds tested showed anti-proliferative activity, with one, compound 22, inhibiting both Philadelphia chromosome negative REH and Philadelphia chromosome positive SupB15 ALL cell division. The novel advantage of these compounds is the potential synergy with standard chemotherapeutic agents, while concomitantly blunting the emergence of dyslipidemia. Thus, the cylopropanecarboxamides represent a novel class of compounds that can be potentially used in combination with the present standard-of-care to limit treatment associated dyslipidemia in ALL patients.
Nair Rajesh R; Geldenhuys Werner J; Piktel Debbie; Sadana Prabodh; Gibson Laura F
Bioorganic & medicinal chemistry letters
2018
2018-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bmcl.2018.03.061" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2018.03.061</a>
Perceptions of child protective services among pregnant or recently pregnant, opioid-using women in substance abuse treatment.
Barriers to substance abuse treatment; Child protective services; Opioid dependence; Pregnancy
Pregnant, opioid-using women represent a challenge to healthcare providers attempting to engage them in prenatal and substance abuse services. Limited, primarily international research suggests that child welfare clients have mixed feelings about Child Protective Services (CPS) and that fear of CPS may present a barrier to care. Understanding how pregnant opioid-using women in substance abuse treatment perceive CPS may be useful in encouraging substance abuse treatment initiation. Participants were currently or recently (within past 12 months) pregnant women with current or recent (within past 12 months) abuse/dependence of pharmaceutical opioids at a drug treatment facility. Participants were recruited by treatment staff to participate in a comprehensive study across multiple domains. Data for this analysis were collected using semi-structured qualitative interviews. Transcribed data were thematically analyzed using in vivo and interpretive coding by three coders for purposes of inter-rater reliability. Following 2, two-hour meetings, consensus was reached on primary themes and sub-themes. Two major themes and several sub-themes were identified: 1) Participants' feelings and attitudes about CPS (positive and negative); 2) Interaction-based perceptions of CPS' function and performance. Participants' feelings toward CPS were often conditioned by their experiences with individual caseworkers. While many pregnant, opioid-using women identify legitimate, and even useful features of CPS, fear of CPS can be a barrier to care. Making substance abuse treatment accessible to this population requires recognition of their complex feelings toward CPS, and coordination among CPS case workers and substance abuse treatment providers.
Falletta Lynn; Hamilton Kelsey; Fischbein Rebecca; Aultman Julie; Kinney Beth; Kenne Deric
Child abuse & neglect
2018
2018-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.chiabu.2018.01.026" target="_blank" rel="noreferrer noopener">10.1016/j.chiabu.2018.01.026</a>
A broader understanding of care managers' attitudes of advance care planning: A concurrent nested design.
*Attitude of Health Personnel; *Health Knowledge; Adult; Advance Care Planning; Advance Care Planning/*standards; Attitudes; Case Managers; Chi Square Test; community health; Concurrent Prospective Studies; Convenience Sample; decision-making; Discussion; end of life; Female; Focus Groups; Funding Source; Health Services Accessibility/standards; Human; Humans; Male; Middle Age; Middle Aged; Midwestern United States; Multicenter Studies; Multimethod Studies; Nurse Attitudes; nurses; Practice; qualitative; Qualitative Research; quantitative; Questionnaires; Surveys; Surveys and Questionnaires; Thematic Analysis
AIMS AND OBJECTIVES: To examine barriers of advance care planning (ACP) experienced by care managers (CMs) through a mixed methods approach. A concurrent nested design was used to acquire a deeper understanding of ACP and to identify nuances between quantitative and qualitative data. BACKGROUND: Past quantitative studies on providers have identified barriers related to time, culture, knowledge, responsibility and availability of legal documents. These barriers, and accompanying attitudes and feelings, have been taken at face value without rich qualitative data to identify under what conditions and to what extent a barrier impacts care. DESIGN: A two-part multisite, mixed methods study was conducted using surveys and focus groups. METHODS: Surveys were completed by 458 CMs at 10 Area Agencies on Aging and 62 participated in one of eight focus groups. Data were analysed using a concurrent nested design with individual data analysis and a merged data approach. RESULTS: There were three main distinctions between the quantitative and qualitative data. First, while CMs reported on the survey that ACP was not too time consuming, focus group data revealed that time was an issue especially related to competing priorities. Second on the survey 60% of the CMS reported they had enough knowledge, but qualitative data revealed about more nuances. Last, the reported comfort levels in the quantitative data were less overt in the qualitative date where additional feelings and attitudes were revealed, for example, frustration with families, preferences for more physician involvement. CONCLUSIONS: Care managers reported their attitudes about ACP, clarified through a rigorous mixed methods analysis. Care managers can successfully lead ACP discussions, but require further education, resources and team-based guidance. RELEVANCE TO CLINICAL PRACTICE: Advance care planning is essential for reducing emotional, social and financial burdens associated with healthcare decision-making, and CMs can positively impact ACP discussions when appropriately supported by the clinical community. The many nuances in the ACP process that we found illustrate the need for ongoing discussions, education and research on this important topic.
Aultman Julie; Baughman Kristin R; Ludwick Ruth
Journal of clinical nursing
2018
2018-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/jocn.14531" target="_blank" rel="noreferrer noopener">10.1111/jocn.14531</a>
A Comparison of Participants in Two Community-Based Programs: Assisted Outpatient Treatment and a Mental Health Court.
Assisted Outpatient Treatment; mental health courts; Outpatient commitment
OBJECTIVE: Mental health courts and assisted outpatient treatment (AOT) are tools to help people with serious mental illness engage in treatment and avoid or reduce institutionalization. As both programs become increasingly prevalent, questions remain about whether people with severe mental illness who receive AOT have the same characteristics, histories, and service needs as those who participate in mental health courts. If there are differences, each program may require assessments and interventions tailored to the specific characteristics and needs of participants. METHODS: This study examined administrative criminal justice and mental health services data for 261 people with serious mental illness who participated in AOT, a mental health court, or both over seven years. RESULTS: Three percent of the sample participated in both programs. Compared with participants in mental health court, participants in AOT were older, less likely to have an alcohol use disorder, and more likely to have a schizophrenia spectrum disorder than a bipolar disorder. The participants' histories of crisis mental health service utilization, hospitalization, and incarceration prior to program entry varied significantly by program. CONCLUSIONS: The findings suggest that there are differences among individuals with serious mental illness who are served by AOT and mental health court programs. AOT participants had greater engagement with mental health services, and a significant portion of AOT participants also had a prior criminal history that placed them at risk of future justice involvement. Program administrators need to recognize and address the clinical and criminogenic needs that place individuals at risk of becoming hospitalized and incarcerated.
Bonfine Natalie; Ritter Christian; Teller Jennifer L S; Munetz Mark R
Psychiatric services (Washington, D.C.)
2018
2018-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1176/appi.ps.201700341" target="_blank" rel="noreferrer noopener">10.1176/appi.ps.201700341</a>
Twin-twin transfusion syndrome screening and diagnosis in the United States: A triangulation design of patient experiences.
Adult; Female; Humans; Retrospective Studies; Ultrasonography; Cross-Sectional Studies; Fetofetal Transfusion/*diagnosis/*diagnostic imaging/*epidemiology; Gestational Age; Patient Reported Outcome Measures; Pregnancy; Prenatal Care/methods; Ultrasonography/methods; United States; Prenatal/methods
OBJECTIVE: Using patient-reported experiences, this study: 1) quantitatively evaluated TTTS screening trends, 2) examined screening and diagnostic experiences using a mixed methods approach, and 3) determined gaps in clinical care experiences. DESIGN: This was a cross-sectional study. Data was collected using a self-report, retrospective survey. A triangulation design was used to validate quantitative survey data with thematically analyzed qualitative data. SETTING: Participants were recruited through social media and national foundations and completed the survey online. PARTICIPANTS: Participants were 312 women who completed a TTTS pregnancy in the United States, representing the largest survey of participants who have experienced TTTS. METHODS: Descriptive statistics and bivariate analyses were conducted. Multivariate logistic regression examined predictors of ultrasound frequency. Qualitative data were initially coded by hand and checked using qualitative software. RESULTS: The percentages of participants reporting guideline recommended screening, including identification of pregnancy type by gestational week 13 and timely receipt of ultrasounds, increased over time. However, 44.6% of participants diagnosed in recent years (2014 and later), reported that prior to TTTS diagnosis, they did not receive biweekly or more frequent ultrasounds. Three patient-reported provider practices were related to receiving ultrasounds at the recommended frequency: (1) determining MCDA status prior to gestational week 14, (2) providing participants with early warnings about the risk of TTTS to their pregnancies after MCDA status had been determined, and (3) referring participants to a Maternal-Fetal Medicine Specialist after MCDA identification, as validated by qualitative data. Our qualitative data revealed gaps in effective clinical care experiences among OB/GYN and specialist providers. CONCLUSION: These findings indicate screening and diagnosis for TTTS, as reported by patients, is improving in the United States; however, further efforts are required to ensure all patients receive appropriate screening, education and a team-based approach to comprehensive and supportive clinical care.
Fischbein Rebecca; Nicholas Lauren; Aultman Julie; Baughman Kristin; Falletta Lynn
PloS one
2018
1905-7
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1371/journal.pone.0200087" target="_blank" rel="noreferrer noopener">10.1371/journal.pone.0200087</a>